2022 Ingredient trends for food, drinks, dietary supplements, and natural products

The fight between the supplements industry and FDA over the ingredient NAC will heat up in 2022

Cognitive function is now a mainstream market with strong growth

AOAC International (Rockville, MD) and the Global Retailer and Manufacturer Alliance (GRMA; King of Prussia, PA) has signed a memorandum of understanding (MOU) that establishes a strategic partnership for the advancement of their shared goals of consumer product safety standards. Signed in December of 2021, the MOU outlines how the two organizations will work together to develop and promote quality initiatives within select health and wellness categories, with an initial focus on botanicals, dietary supplements, colors, and cosmetics.

“We are very excited to work with GRMA and its many global members who engage with millions of consumers around the world,” said David B. Schmidt, AOAC executive director, in a press release. “AOAC’s standards and methods will provide a substantial foundation to ensuring these consumers receive the safest products with the components they expect.”

AOAC and GRMA will work together on task forces, committees, and working groups, including AOAC’s new Botanical and Dietary Supplement Product Integrity Program, and GRMA’s recently formed Dietary Supplement Integrity Committee.

“We are excited by the opportunity to collaborate with AOAC International across a number of initiatives. They have a well-established and technical approach that provides solutions to some areas of concern for our stakeholders,” said Allyn Shultis, GRMA executive director. “In the initial thought leader discussion, we had near-record level participation and valued input from manufacturers, retailers, certifying bodies, and other key industry stakeholders. From that meeting, we see several ways to provide significant value to our members, the industry, and consumers. Through our shared appreciation of the consensus standard process, our next meeting will focus on prioritizing the opportunities and initiatives identified by industry stakeholders within this collaborative framework.”

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AOAC International and the Global Retailer and Manufacturer Alliance has signed a memorandum of understanding (MOU) that establishes a strategic partnership for the advancement of their shared goals of consumer product safety standards.

AOAC International and GRMA announce partnership to advance product safety goals

Certifications by Nutrasource Feature Wall in lobby. Image courtesy of Nutrasource.

Nutrasource Pharmaceutical and Nutraceutical Services (Guelph, ON, Canada) has complete a 3,000 square foot expansion of its main facility in Guelph, Ontario. The expansion brings in seven new offices, 10 workstations, a boardroom, and a significant upgrade to the sample processing room, which has been tripled in size.

“Throughout this pandemic, our team has remained ‘Nutrastrong’ and intact. In fact, we grew our staffing compliment during this time,” said Will Rowe, president and CEO of Nutrasource. “Even with the uncertainties we are still facing, we continue to grow and expand for teams, tools and infrastructure to support our global clientele.

“This expansion was something we were looking to do last year, but with COVID, we didn’t know what to expect, and what our workforce would look like,” continued Rowe. “We are excited to be able to provide a new designated work area for the Certifications by Nutrasource department, additional rooms for our clinical trials group and expanded workspace for our staff.”

The expansion brings in seven new offices, 10 workstations, a boardroom, and a significant upgrade to the sample processing room, which has been tripled in size. 

Nutrasource completes 3,000 square foot expansion

Haley Gershon is marketing manager for Beta Analytic Inc. (Miami; 

Cinnamon bark oil is commonly used as a fragrance and flavoring agent. Although companies often market their products to include naturally sourced cinnamon bark oil, the industry faces a high risk of fraudulent claims due to acts of economically motivated adulteration.

 In an effort to steer clear of ingredient adulteration, both manufacturers and distributors are implementing authenticity testing as part of their quality assurance and quality control procedures.

To ensure cinnamon bark oil is authentic and derived from plant-based sources, carbon-14 analysis is employed to differentiate between biomass-derived (biobased) and petrochemical-derived ingredients.

Risks of Economically Motivated Adulteration

Economic adulteration occurs in several industries in the natural products sector, including the flavor and fragrance industry. Economically motivated adulteration (EMA), often known as food fraud, refers to the intentional adulteration of ingredients, with the goal of financial gain or advantages.

 This phrase can refer to the addition, substitution, or dilution of ingredients as means of adulteration.

Cinnamon bark oil is a common flavor and fragrance ingredient that is often used as a spice. The global cinnamon oil market is expected to grow at a compound annual growth rate of 3.6% between 2018 and 2025, forecasted to increase from a value of USD $100 million to USD $130 million USD.

 Given cinnamon bark oil’s high demand and high production costs, the ingredient runs the risk of being adulterated with a less expensive alternative such as synthetic cinnamon leaf oil, synthetic cassia oil, or cinnamaldehyde.

Detecting EMA is a challenge to the food industry. This calls for analytical methods such as carbon-14 analysis to verify whether or not flavor and fragrance ingredients, like cinnamon bark oil, are authentically derived from biomass-based material. By analyzing cinnamon bark oil using carbon-14 analysis, it is possible to verify whether cinnamon oil was formulated from its natural source or if it was adulterated using synthetic petrochemical-derived cinnamaldehyde.

Carbon-14 testing is an analytical tool used to differentiate between biomass-derived and petrochemical-derived ingredients. Any product or ingredient sourced from plants, animals, or microbiological materials contains a measurable amount of the radioactive isotope carbon-14. Ingredients sourced entirely from petroleum-derived material, meanwhile, do not contain any amount of carbon-14.

Carbon-14 analysis uses an accelerator mass spectrometer (AMS) instrument to measure the exact percentage of carbon in a material that comes from biomass, according to international standards such as ASTM D6866 or ISO 16620-2.

ASTM D6866 is a standard that was developed in the United States that is used to determine the biobased content of solid, liquid, and gaseous material. This standard reports results as a percentage to indicate the portion of a product, such as a flavor, fragrance, food, or beverage, that is of biobased sources compared to petrochemical-derived synthetic sources.

 Likewise, the ISO 16620-2 standard uses carbon-14 analysis as a method to determine the biobased content of solid, liquid, and gaseous samples. ISO 16620-2 is applicable for various sample types, including flavors, fragrances, food, and beverages.

Carbon-14 test results will yield a percentage to indicate the portion of a sample tested that is derived from biobased content.

The prevalence of adulteration has made it critical for stakeholders throughout the supply chain to detect fraudulent products and ingredients. Submitting products for analysis by a third-party laboratory is a critical step for manufacturers and distributors to strengthen quality control procedures and maintain product quality.

 Although carbon-14 analysis cannot distinguish between different natural-derived sources, it is a reliable analysis for verifying whether a sample is biomass-derived, petrochemical-derived, or a mixture of the two sources.

Within the food and beverage industry, carbon-14 analysis is useful in both authenticating ingredients that are biomass-derived and in verifying ingredient adulteration using petrochemical synthetic ingredients. For instance, if a sample of cinnamon bark oil with a label claim of “all-natural ingredients” is measured using the analysis and reports a result of 100% biobased content, this indicates that the sample is wholly derived from biomass sources, authenticating the all-natural label claim. However, if a cinnamon bark oil sample with the same “all-natural ingredients” label is analyzed and reports a result that falls between 0% and 100% biobased content, this means the sample is a mixture of petrochemical-derived and biomass-derived sources, demonstrating a case of ingredient adulteration and mislabeling. Furthermore, if a carbon-14 test result yields a report of 0% biobased content, this indicates the sample is fully derived from petrochemical sources and therefore does not contain any naturally sourced material.

As a result, carbon-14 analysis plays an important role in a company’s quality control and quality assurance process.

As a result of the genuine ingredient’s high demand and high price, cinnamon bark oil is vulnerable to adulteration. Although threatened by economically motivated adulteration, establishing robust quality control programs throughout the supply chain can lessen the potential of ingredient fraud cases within the flavors and fragrance industry. Submitting samples for routine analysis such as carbon-14 testing allows manufacturers and suppliers to verify early on whether ingredients like cinnamon bark oil are derived from biomass or petrochemical sources.

Food Fraud and ‘Economically Motivated Adulteration’ of Food and Food Ingredients.

” Congressional Research Service report. Published January 10, 2014. 

Cinnamon Oil Market Size and Forecast in Global by Product Type and End-User and Regions (Countries) 2016-2026)

Handbook of Herbs and Spices, Second Edition. 

ASTM D6866 - 21, Standard Test Methods for Determining the Biobased Content of Solid, Liquid, and Gaseous Samples Using Radiocarbon Analysis

International Organization for Standardization. “

ISO 16620-2:2019, Plastics – Biobased content – Part 2: Determination of biobased carbon content

Although companies often market their products to include naturally sourced cinnamon bark oil, the industry faces a high risk of fraudulent claims due to acts of economically motivated adulteration.

Cinnamon bark oil: Carbon-14 testing helps catch adulteration

 investigated the immune health-modulating effects of black seed oil and vitamin D3 on mesenchymal stem cells (MSCs) and on mice. MSCs can modulate inflammatory responses and sense different inflammatory signals. Two different black seed oils were used in the study: ThymoQuin (TQ), standardized to 3% thymoquinone and low free fatty acid, from Israel-based TriNutra, and a commercial black seed oil (CBSO) high in free fatty acid content.

 portion of the study, MSCs were treated with TQ alone, CBSO alone, vitamin D3 alone, TQ with vitamin D3, and CBSO with vitamin D3 to examine the effects of each on MSC proliferation levels of inflammatory biomarkers, changes in lipid droplet number and size, adipocyte differentiation, mitochondrial biogenesis, and stem cell function. Researchers found that CBSO significantly increased average lipid droplet size when compared to control, while TQ reduced average lipid droplet size, even more so than vitamin D3 alone. The combination of TQ and vitamin D3 showed significant reductions in average lipid droplet size. 

While CBSO increased TNF-alpha levels, TQ reduced the expression of the inflammatory cytokine. Overall, TQ reduced the size of large lipid droplets and effectively increased small lipid droplet area, and these effects were enhanced with the addition of vitamin D3. Researchers also observed increased mitochondrial biogenesis and energy metabolism in the presence of TQ, which was only enhanced with vitamin D3.

In the animal protocol, 20 mice were divided into five groups: 1) lean controls, 2) high fat diet (HFD), 3) HFD and treated for eight weeks with TQ, 4) HFD and treated for eight weeks with vitamin D3, and 5) HFD and treated for eight weeks with TQ and vitamin D3. After assessing angiogenesis in mouse liver tissue, researchers found that mice eating a HFD with TQ and vitamin D3 had higher levels of the antibodies ANG-1 and SDF-1, while the HFD diet alone had the lowest levels of those antibodies, demonstrating a influence on the immune system.

“I have long discussed the synergistic properties that are unique to black seed oil standardized to 3% thymoquinone and with very low free fatty acids,” said Morris Zelkha, co-founder and CEO of TriNutra, in a press release. “While previous focus has been mainly on its synergy with omega-3s, we are happy to share the results of ThymoQuin combined with vitamin D3 for improved immune support. Vitamin D3 is commonly recognized as a necessary part of good health, so seeing that we can enhance its effects with ThymoQuin opens a lot of possibilities for new products and further research.”

Yeun K et al. “Beneficial effect of 3% thymoquinone on stem-cell-mediated improvement in immune system and anti-inflammatory function.” 

When combined with vitamin D3, ThymoQuin reduced inflammatory biomarkers and upregulated immune response.

Study demonstrates synergy between the standardized black seed oil ThymoQuin and vitamin D3

Jennifer Grebow is the editor-in-chief of 

, an award-winning media-content provider in the dietary supplement and natural products market. 

, an MJH Life Sciences brand, provides insights and industry updates critical to manufacturers of dietary supplements, healthy foods, and nutritious beverages. 

 keeps industry abreast of current market trends, research updates, news, and regulatory developments. 

goes beyond the 24-hour news cycle and provides in-depth analysis to help industry players navigate the challenges and changes in the near- and long-term. 

, the largest privately held, independent, full-service medical media company in North America, dedicated to delivering trusted health care news across multiple channels.

N-acetyl-L-cysteine (NAC) may not be a familiar ingredient to some dietary supplement users, but within the supplements industry—and among those who regularly take NAC supplements for 

antioxidant, liver, and respiratory support

—NAC is now a red-hot topic thanks to recent regulatory actions taken by U.S. FDA. In 2022, expect further discussion about NAC and possible friction between FDA and the industry leaders confronting the agency to protect the supplement industry from what they say is FDA’s misapplication of the law.

First, some background: Within the Federal Food, Drug, and Cosmetic Act (FD&C Act) governing dietary supplements in the U.S. is an infamous “drug exclusion provision” (Section 201(ff)(3)(B)(i)). This provision was signed into law on October 15, 1994, as part of the Dietary Supplement Health and Education Act (DSHEA) that amended the FD&C Act with new regulations for dietary supplements.

 that dietary supplements may not include “an article authorized for investigation as a new drug, antibiotic, or biological for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public.” In other words, if an ingredient was first approved as a drug, or studied as an investigational new drug (IND) and that research was made public, supplement companies thereafter could not begin selling the ingredient as a dietary supplement—in essence, protecting drug companies’ research investment from supplement companies turning around and selling that same ingredient in lower-cost supplements. If the ingredient 

, however, sold as a dietary supplement before the ingredient was publicly investigated or approved as a new drug, supplement companies could legally continue selling the ingredient as a dietary supplement.

Several drug and supplement ingredients lawfully coexist in the market under the drug exclusion provision. Omega-3 fish oil is one. The Natural Products Association (NPA; Washington, DC) points to 

FDA has also used the drug exclusion provision to challenge the legal status of certain dietary supplement ingredients. In 2016, for instance, FDA declared that vinpocetine, already a longtime ingredient in the supplements market, was now 

N-acetyl-L-cysteine is the latest ingredient in FDA’s crosshairs involving the drug exclusion provision. In July 2020, FDA sent 

 to a handful of companies selling products as dietary supplements, some as hangover remedies. In those warning letters, FDA claimed that NAC was approved as a new drug in 1963 and that there are no records showing that NAC was marketed in supplements prior to then.

Supplement industry leaders rebutted FDA’s reasoning in citizen petitions filed by 

, plus comments on these petitions from the American Herbal Products Association (AHPA; Silver Spring, MD)

First, pointed out CRN and NPA in their petitions, as well as AHPA in its comments, the NAC article approved as a drug in 1963 is different from the article that’s sold as a supplement. The drug approved in 1963 was an inhaled drug and not a substance to be orally consumed. In fact, an oral NAC drug was not approved for use until 2016, long after NAC oral supplements entered the market, both CRN and AHPA stated

, NPA said it remains “unclear” whether an ingredient can be excluded from the definition of a dietary supplement “when the article has been approved as a drug not intended to be administered by ingestion.”

Second, CRN and NPA wrote in their citizen petitions, evidence substantiating the 1963 drug approval or public records showing investigation as a new drug are shaky. NPA wrote

, “Usually, evidence from the period of time in question are handwritten notes and documents.” In a December 2020 letter

 on the matter to Steven Tave, then-director of FDA’s Office of Dietary Supplement Programs, CRN wrote, “This handwritten notation [indicating a drug approval date of 1963] raises a number of questions about the reliability of this record, not the least of which is whether the approval date was actually 1963 or sometime later, why was the approval date handwritten, when was the notation made, and who made it. This is not the type of document that should be regarded as authentic.”

CRN pointedly added: “The unreliability of a handwritten date is exactly the type of issue that FDA likely would raise for a dietary supplement company providing similar evidence that an ingredient was marketed as a supplement before being approved as a drug.”

Third, the associations said, evidence—including documentation AHPA cited in its comments to FDA

—shows that NAC was on the market as a supplement before the drug exclusion provision became law when DSHEA passed in October 1994.

Michael McGuffin, AHPA’s president, explains to 

 “AHPA submitted comments to FDA wherein we identified a number of dietary supplements being marketed with NAC as an ingredient prior to the enactment of DSHEA. Following our comments, FDA issued a formal request for information, stating their interest in receiving ‘data and information on the earliest date that NAC was marketed as a dietary supplement or as a food, the safe use of NAC in products marketed as a dietary supplement, and any safety concerns.’ Since submitting our initial comments, we have found documentation of NAC marketed as an ingredient in a food product, and intend to provide the information to FDA.”

Most critically, these industry leaders argue that the drug exclusion provision, which was enacted with DSHEA’s passage in October 1994, is not allowed to be applied in order to retroactively pull off the market ingredients that were already on the market prior to the provision’s passage. In CRN’s letter to FDA’s Tave, the association wrote

 that “the definitional exclusion established by section 201(ff)(3)(B)(i) should be read to have 

 prohibited products containing articles that were approved as new drugs 

 October 25, 1994, from being marketed as dietary substances, unless such articles were marketed in dietary supplements prior to approval. By contrast, section 201(ff)(3)(B)(i) should only be read to 

 apply to products containing articles that were approved as new drugs 

 October 25, 1994, if Congress expressed a clear, unambiguous intent for this provision to have a retroactive effect.”

Clearly, Congress did not expressly intend for the drug exclusion provision to act retroactively, CRN extensively explained in its citizen petition based on its review of both DSHEA and the provision’s legislative history.

 “If these ingredients were on the market pre-DSHEA passage in 1994, FDA doesn’t have the authority to remove them,” Megan Olsen, CRN’s vice president and associate general counsel, tells 

“Congress never gave that intent, and there’s strong legal argument that when Congress does not give a clear, unambiguous intent that a statute is intended to be applied retroactively, then it cannot be applied retroactively.”

McGuffin says the same: “Congress did not intend for DSHEA to be retroactive. Rather, DSHEA was intended to incentivize drug research on ingredients first brought to market…—not in the past, but in the future. Any contrary interpretation is, at best, strained.”

Olsen adds that “the purpose of this provision, and this bears itself out in the legislative history, was to encourage drug development and protect drug investment. You’re encouraging development by protecting those investments and helping ensure to drug companies that they wouldn’t have to be concerned about putting investment in and then have a supplement come on the market.” In the case of NAC drugs and supplements, “those arguments aren’t available,” she says, because both coexisted in the market prior to the passage of DSHEA’s drug exclusion provision. “It’s concerning that you would apply it retroactively when drug companies would never have any assurances that there would be a protection,” she adds. “If a supplement is already on the market and a drug company also gets that ingredient approved in a drug, the supplement doesn’t come off the market. It’s not, ‘Okay, now that the drug is here, you no longer can sell the supplement.’”

“It’s important that the FDA is interpreting 

of the provisions in a manner that is consistent with Congressional intent,” she says. “And I think here, we very much are concerned that the way that they’re using it does 

Supplement leaders are adamant about defending the industry from FDA’s turn on NAC because FDA’s actions could set a dangerous precedent in the supplements industry for years to come.

McGuffin says, “If FDA bans NAC by retroactively applying the drug exclusion clause, there is concern that the agency could do the same with any vitamin, mineral, or herb that has ever been the subject of any formal drug investigation.”

Daniel Fabricant, PhD, NPA’s CEO and president, tells 

It’s incredibly concerning if FDA can retroactively apply the drug exclusion clause. DSHEA was introduced to balance consumer access to nutritional supplements and strong federal oversight of the industry. However, what we are seeing with NAC is unnecessary federal intervention. NAC has been on the market for over three decades, and there are more than 800 NAC product labels in the [National Institutes of Health’s] Dietary Supplement Label Database. These products have been safely on the market, so what’s to say FDA wouldn’t respond this way for other ingredients? Vitamin C and other dietary supplements have been on the market as drugs. So, this action gives way to FDA arbitrarily using the drug exclusion clause as an administrative procedure disrupter to business.”

Imagine the unstable environment supplement companies face if, at any point, someone could introduce obscure evidence long buried to threaten the existence of a supplement decades later. Consider that documentation of clinical trials done long ago is often publicly unavailable or unreliable. “It becomes almost 

when you’re looking back decades for a company to readily determine what types of drugs were included,” Olsen points out. And, she says, “I think there’s concern that FDA, which 

have records, but you almost have to FOIA [Freedom of Information Act] those records, could turn around and say, ‘Hey, five years from now, well, this ingredient is precluded because there were drug trials in the 1980s.’”

How can a supplement company confidently move forward amidst that kind of uncertainty? It’s unfair to supplement companies for FDA to do a 360 on an ingredient like NAC, leaders say.

“Here, FDA has implemented a sudden policy change without providing a well-reasoned explanation, and has done so in a manner that will affect thousands of industry and consumer stakeholders…,” CRN’s letter to Tave

 pointed out. “As noted above, prior to July 2020, it was FDA’s longstanding policy to permit the marketing of dietary supplements containing NAC. FDA had reviewed over 100 30-day notifications of structure/function claims for NAC and never raised any issues with the drug preclusion clause. FDA also had reviewed a qualified health claim for NAC and failed to raise the drug preclusion clause. As part of the qualified health claim review process, FDA specifically assesses whether the substance that is the subject of the qualified health claim qualifies as a food or dietary ingredient in dietary supplements. In response to the qualified health claim petition involving NAC, FDA states that NAC is a dietary supplement.”

Olsen says, “There are other legal concerns or other legal doctrines that say that after so long of allowing companies to rely on FDA’s position, FDA can’t reverse that position without significant reason.”

Why is FDA going after NAC? After all, safety concerns about NAC aren’t popping up, to industry’s knowledge. Says NPA’s Fabricant, “Our members go to great lengths to provide consumers with safe products. We know NAC is safe, but if FDA has data points that suggest otherwise, they need to communicate those findings to us, which they haven’t.”

Olsen says, “When FDA has raised concerns about the legality of ingredients as dietary supplements in the past, we often see those concerns tied to safety issues. For example, with vinpocetine, FDA in 2019 

 about the use of the ingredient by women of childbearing age. FDA, however, has not banned the use of vinpocetine as a dietary ingredient. FDA also maintains a 

Dietary Supplement Ingredient Advisory List

 regarding dietary ingredients the agency has indicated ‘do not appear to be lawful.’ For the ingredients on this list, FDA has generally flagged safety concerns about the ingredient. This list is not a final determination of legality or safety by FDA, but a common concern in FDA evaluation of a dietary ingredient’s legality is safety. What is so striking here for NAC—FDA has never, that we are aware of, questioned the safety of NAC in dietary supplements. The ingredient has a decades-long history of safe use, and its safety record has been acknowledged by other authoritative government bodies like the National Institutes of Health (NIH), which noted in a recent 

 that ‘[n]o safety concerns have been reported for products labeled as dietary supplements that contain NAC.’”

Industry leaders are demanding that FDA defend its reversal on NAC. They want answers. So far, they haven’t gotten them, leading associations to take more aggressive steps. This fight will persist in 2022.

 to CRN’s citizen petition. Instead of addressing the petition’s legal questions, FDA’s letter simply asked for more proof of NAC’s market history as a supplement—which, Olsen says, “is information we think is irrelevant to answering the legal questions that CRN has posed.” CRN, she says, “asked the agency solely to review and defend legal arguments and legal concerns with the validity of their July 2020 position on NAC,” which she says thus far the agency has failed to do.

Frustrated with FDA’s lackluster reply, this January 

 criticizing the agency, stating, “The agency’s nonresponsive November 24

response does not address the single legal issue first raised by CRN in December 2020 and restated in CRN’s June 1

citizen petition: whether the drug preclusion provision in section 201(ff)(3)(B)(i) properly precludes NAC from being marketed in dietary supplements.”

, stated: “To AHPA’s knowledge, FDA has not expressly addressed the question of whether DSHEA, and the prior drug exclusion provision in particular, has retroactive effect.”

Following lack of response to NPA’s citizen petition, in December 2021 NPA took the strong step of 

 to “hold unlawful and set aside FDA’s final actions that are arbitrary, capricious, an abuse of discretion, and contrary to law.”

“NPA will leave no stone unturned until FDA’s decision is reversed.”

How many NAC companies and products today are adversely impacted by FDA’s reversal? AHPA’s McGuffin points out, “At least 600 products with NAC as an ingredient can be found in the National Institutes of Health’s Dietary Supplement Label Database (DSLD), the public database for volunteer product listing of dietary supplements.”

“NAC supplement sales are very significant for the industry,” Fabricant tells 

, adding that the ingredient is sold both domestically and internationally. He adds: “NAC has been safely on the market for decades, and the agency should know this because they have the data to back it up. Over 800 labels accompanied by product information, including claims, are available to them through the NIH Dietary Supplement Label Database.”

 asked market researcher SPINS (Chicago) to provide an estimate on NAC market sales in the supplement channels it tracks. Sales appear to be growing.

“N-acetyl-L-cysteine saw 61% growth in sales in 2021 compared to 2020,” says Haleigh Resetar, SPINS corporate communications specialist. “The fastest-growing categories include performance nutrition—specifically hydration and electrolyte—and condition-specific supplement formulas, including cognitive health supplements and organ support supplements.” Performance nutrition is definitely a key market, adds CRN, citing data from SPINS multioutlet (MULO) channel tracking, powered by IRI (Chicago), and SPINS natural enhanced channel tracking, showing NAC supplement sales for performance nutrition up 98% over a year ago.

Resetar’s colleague at SPINS, Senior Market Insights Analyst Scott Dicker, says, “We are seeing a lot of growth for NAC in the MULO plus convenience channel, the natural enhanced channel, as well as some in [the] regional [independent grocery channel] as well. The dollar volume isn’t high in it, but we’re definitely seeing a lot of consumers interested in it.”

FDA’s adverse opinion on NAC’s legal status—which, it’s key to note, is only mentioned in warning letters and is not an official policy change—has already negatively impacted NAC supplements on the market. NAC supplements are sold by respected brands including NOW Foods, Thorne, Pure Encapsulations, and Life Extension, to name a few. 

 that Amazon.com had ceased allowing NAC products to be sold on its website.

 “We have heard of other e-commerce platforms prohibiting the sale of NAC on their platform, and financial service providers restricting transactions related to NAC.”

“We understand that some contract manufacturers have also indicated that they do not want to continue to manufacture NAC. So, there are real-world implications that are happening here,” Olsen adds. “And we’ve heard directly from consumers, we’ve heard from healthcare practitioners that sell these products to patients or work with patients to secure these products, that there’s a concern out there that consumers rely on these products as dietary supplements for their health, and they’re having trouble accessing the products because either Amazon or companies are deciding to limit or stop their inventory.”

SPINS’s Dicker says that while NAC might not be a flagship product for some brands, it’s likely still an important one given the rising consumer interest. During the pandemic, he says, while brands might have started cutting the “tail” off their product lines and discontinuing less-popular products, NAC probably remained a priority. “With something growing in popularity like NAC, it could become a more major role in their business, so that is definitely something to consider as well, those financial implications” of any FDA actions, Dicker says.

Unfortunately, because FDA’s opinions are still not official legal action and only mentioned in the warning letters, NAC companies have few options for recourse at this point, even as they see tanking sales, Olsen points out. “Warning letters are not final agency action, and that positioned has been

established by both FDA and the courts,” she says. “And so, it doesn’t give companies the opportunity, like they would where there’s actually legal consequences that have flowed out of an FDA action, to take that action to court.”

For now, she says, “Companies need to assess their own risk of selling NAC. CRN considers this still a 

open matter. We have seen FDA reverse its position in warning letters in the past.” So perhaps there’s hope.

Will some in the industry end up calling on Congress to intervene? As McGuffin says, “AHPA and the industry are doing what we can to ensure safe and informed consumer access to NAC. We are evaluating every avenue. The actions taken so far—two citizen petitions, comments by AHPA, the lawsuit against FDA—may help, but we might have to seek a solution in the Congress.”

What’s more, he says, given FDA’s attempt to use the drug exclusion provision to remove a supplement from the market once again, it may be time to reexamine this provision altogether. “If the dietary supplement industry brings a new ingredient to market first, we share the market with the drug industry. However, if the drug industry initiates research on a new ingredient, the dietary supplement industry is shut out. It is time for Congress to reconsider the drug exclusion clause, a restrictive provision of DSHEA that impacts consumer access and choice, and apply congressional pressure to FDA accordingly.”

reported that U.S. Senator Michael Lee (R-UT) requested a FDA hearing on the NAC issue but was denied.

 Says Fabricant, “When you have not one, but two members of Congress, request more information about NAC, and the agency ignores their questions, it’s a sign of disrespect. Congress has oversight over agencies like the FDA. FDA’s actions have put them under a microscope, and Congress is exploring legislative measures to make them more transparent. It’s a strenuous time at the FDA for several reasons, and we understand that. However, when you become less and less transparent with the industry, it will rightfully raise concerns. I’m confident we will see more congressional action in the coming months that demand more accountability from the FDA.”

What could ultimately happen? “If FDA maintains its position that NAC isn’t a legal dietary ingredient, it would need to begin taking enforcement actions against companies selling,” Fabricant continues. “Given their posturing with [cannabidiol] CBD, and considering NAC’s safety record, I have a hard time believing FDA would begin seizing products or using other enforcement action.”

Dietary supplement associations will continue fighting FDA on the matter this year. Says Olsen, “CRN doesn’t consider this a settled battle while the agency continues to deliberate as to what their response will be.”

In the meantime, “We’ll probably see more actions taking place in the fight over NAC,” says Fabricant.

It’s a fight worth having, he and the others say. “This issue is more important than just NAC,” says Fabricant. “FDA’s action sets a dangerous precedent which presents a real and present danger for the dietary supplement industry.”

Everything You Need to Know about NAC, from the Lungs to the Liver

.” Thorne blog. Published April 16, 2020.

Natural Products Association citizen petition to FDA

NDI Draft Guidance: Just When You Thought You Were Safe

Council for Responsible Nutrition citizen petition to FDA. June 1, 2021.

American Herbal Products Associations comments submitted to FDA responding to citizen petitions filed by the 

Council for Responsible Nutrition letter to Steven Tave

, then-director of Office of Dietary Supplement Programs, Center for Food Safety and Applied Nutrition, FDA. December 4, 2020.

Response Letter from FDA Center for Food Safety and Applied Nutrition to Council for Responsible Nutrition

Council for Responsible Nutrition letter to Douglas Stern

, deputy director for regulatory affairs, Center for Food Safety and Applied Nutrition, FDA. January 4, 2022.

Complaint for Declaratory and Injunctive Relief filed by Natural Products Association

Amazon Confirms Plans on Removing NAC Supplements.

FDA Denies Sen. Lee’s Request for Hearing on NAC Supplements

There’s more at stake than just one ingredient in the battle between the supplements industry and FDA over N-acetyl-L-cysteine (NAC).

The fight between the dietary supplement industry and FDA over the ingredient NAC will heat up in 2022: 2022 Ingredient trends for food, drinks, dietary supplements, and natural products

Mental health is getting the attention it deserves as the pandemic and world events pile on stress, anxiety, and depression. But did those concerns outshine focus on other fundamentals of brain health—cognitive functions like memory, focus, and mental endurance? Hardly.

“The cognitive and brain health space has seen immense growth over the past year,” reports Kristen Marshall, digital marketing manager, Verdure Sciences (Noblesville, IN). “From brain function and healthy brain aging to improved memory, mood, emotional wellbeing, stress and anxiety, attention, focus, and mental fatigue, the brain and cognitive market has seen tremendous growth and offered clarity to many consumers while mirroring larger trends for mental health and wellbeing globally.”

As consumers dedicate themselves to improving their health and longevity overall, they’re more eager to maintain cognitive function, too. As Marshall says, “Consumers have dramatically shifted toward proactively tackling health and wellbeing.”

Cognitive function is a priority as the number of seniors grows worldwide. “There is an increasing trend to directly target the aging process,” says Steve Holtby, president and CEO, Soft Gel Technologies Inc. (Los Angeles). “A significant concern associated with growing old is the loss of cognitive function, resulting in dementia. As the brain ages, it becomes more prone to inflammation and oxidation, which causes free radical damage to brain cells. The cumulative effect of free radical damage in the brain over the years as a result of aging can negatively influence cognitive function. This can result in memory loss. In order to reduce the risk of cognitive decline, one must look to improving lifestyle by adopting healthy habits.”

While stress and anxiety might be dominating the pandemic discussion, cognitive function remains a permanent concern. During a December 2021 webcast hosted by private-label food supplements manufacturer PharmaLinea (Ljubljana, Slovenia), guest speaker Monika Szelążek, regional client executive for Euromonitor International (London), said: “When it comes to today’s health problems, they center around stress, anxiety, and sleeping disorders. And this is mainly the outcome of the pandemic, lockdown, and social distancing. However, we believe that in the future, in the long-term perspective, health concerns will change, and memory issues will become one of the most important problems.”

Proactive consumers are seeking out cognitive health products now, including dietary supplements and natural products. The fact that the audience for these products is growing beyond just seniors is exciting.

Younger consumers are looking for ways to improve cognitive function—and we have the pandemic to thank for that, says Scott Dicker, senior market insights analyst for SPINS (Chicago). “First, we saw the wave hit sleep support, mood support, stress relief. And then the next wave is, ‘For my overall wellness, I want to be functioning properly.’ So, we saw this growth in brain-support products as well as in things like performance nutrition as people look for peak performance. But not just in sport. A lot of people are working from home,” he says. “They’re looking at computers a lot. There are a lot more distractions at home. I think we can all agree with that. So, these kinds of brain-support products are growing in popularity as well.”

Dicker’s colleague, Haleigh Resetar, SPINS corporate communications specialist, agrees. “As the movement of working from home has been expanding, there are more distractions facing shoppers during their work hours, so there is a greater need for improving awareness and optimizing concentration.”

Abey Thomas, head of global marketing, Natural Remedies (Bangalore, India), says, “The brain-support market has grown widely beyond simply seniors seeking to preserve basic memory and cognitive function as they age. This market now encompasses gamers, students, and young/middle-age adults who are keenly aware that higher-stressed lives negatively impact their mental performance, so they are seeking supplements and other natural means to sustain cognitive acuity and energy.

“Specifically, there are four growing use segments for this market,” he says. 1) Children (“Approximately one out of 10 children has issues with maintaining focus, energy, and attention. Others deal with learning challenges.”); 2) Young and middle-aged adults (“Millennials have the highest levels of stress among adult generations, and they also represent the largest adult population taking products to support mental health.”); 3) Seniors (“This obvious market group remains a core consumer as the risk of development of mild cognitive impairment becomes more common.”); and 4) Gamers (“Esports…have become one of the globe’s fastest-growing professional sports and requires gamers to develop and utilize extreme mental acuity and concentration.”).

Verdure Sciences’ Marshall says, “We have seen interest in the arenas of mental acuity, mood, memory, focus, attention, concentration, mental fatigue, improved learning, quality of sleep (think: alertness upon waking rather than falling asleep), and more.” She says that “esports/gamers, athletes, children and students, women’s health, as well as an aging population are additional areas of focus.”

Demand for cognitive-support supplements—likely born in the natural retail channel where many trends start—is now moving mainstream. Dicker observes how these product trends develop. “A lot of times, they start in the natural channel. When something’s trending high in natural, we know it’s usually just a matter of time before it becomes a mainstream trend. That’s why, at SPINS, when we look at our natural enhanced channel, that’s really our go-to source for new trends.” Based on growing sales of cognitive supplements SPINS saw in the natural channel, subsequent growth in the mainstream market “was to be expected,” he says.

Resetar agrees. “Any curve in the natural channel will over time migrate into the conventional channel. The natural channel is a great [launchpad] for many new products that are trying to introduce into the market.”

Here’s what we saw happening in the mainstream and natural channels in 2021 in terms of brain supplement ingredient sales in the U.S.

Per SPINS multioutlet channel tracking, powered by market researcher IRI (Chicago), overall sales of cognitive health ingredients in the U.S. mainstream supplements market grew 59% in the year ending October 31, 2021, reaching $366 million compared to $230 million a year ago. By contrast, per SPINS natural enhanced channel tracking, overall sales of cognitive health ingredients in the U.S. natural supplements market grew just 0.2% to $35 million.

This eye-popping growth of 59% in the multioutlet channel shows that cognitive health became a mainstream priority in 2021.

 that cognitive health product sales in 2021 were “still strong despite doubling in 2020 versus 2019.” They say: “We looked at a subset of the most popular-selling supplement formulations for brain health—notably Prevagen, Neuriva, and Focus Factor, and a few niche items—as a surrogate for assessing the popularity and growth trends of all brain health supplements. Looking at the overall growth of these supplements and a few others, we note that, overall, their sales grew by 64% versus a year ago for the 52 weeks ending November 28, 2021. Growth in brick-and-mortar outlets (including food, drug, club, and mass, but excluding Costco and such specialty chains as Vitamin Shoppe) was up 54% in the same period—but for online up a whopping 108%.”

They continue: “Bucking a trend we’ve seen in sales of overall dietary supplements, where sales are split about 50/50 online versus brick-and-mortar, for brain supplements sales appear to be concentrated in brick-and-mortar, totaling about 75%. Perhaps most telling is that these brain supplements taken together show growth of 64%, which substantially outpaces the growth of overall nutritional supplements at 10% versus a year ago for the same period noted earlier.”

What are consumers seeking in their brain-support supplements? To start with, “Consumers are looking for ingredients and finished products that they feel good about purchasing, that contribute to a greater good and offer tangible results,” says Verdure Sciences’ Marshall. Beyond that, she says, “Clean-label, sustainable, traceable, and transparent solutions targeting this space have been successful, especially as value and supply chains face seemingly insurmountable challenges.”

She adds: “Verdure has seen substantial interest in the cognitive/brain category—in particular, formulators and consumers have sought out nootropics, adaptogens, mood and mental acuity solutions, as well as clean-label and transparent offerings with robust stories to support positioning. It is almost assumed that this is all supported by clinical substantiation, third-party certifications, and rigorous quality control and assurance.”

Beverages, gummies, and functional foods are all delivery systems to watch, companies say. Ingredient blends, often in the form of multivitamins, are also a key trend to follow in the brain health supplements market, especially in the mainstream where customers are looking for general solutions.

SPINS’s Dicker says that companies are “working on a lot of synergistic formulas, so what I expect to see—and what we are seeing—are a lot more of these brain health blended products rather than people going for a single ingredient.” Among less-experienced supplement users especially, “when people are searching for things, a lot of times they’re searching just for ‘brain health products’ and not necessarily a lot of these single ingredients, which are sometimes harder to pronounce, sometimes a little harder to search for.”

For instance, SPINS tracking of cognitive health ingredient sales in the U.S. multioutlet channel shows ingredients for brain health multivitamins growing significantly in the year ending October 31, 2021. Breaking that down, SPINS cites 99% growth in cognitive health multivitamins for women and 186% growth in cognitive health multivitamins for men.

Dicker observes, “Multivitamins have historically been a strong supplement category. When people are looking to fill the gaps in their everyday nutrition, that’s a logical first product to take.” Among new supplement users, “instead of maybe adding on a second product, a third product, and building their basket that way, when they see that a multivitamin can also help with brain health and these other functions,” they opt for the multivitamin. “And I don’t think brain health is alone in that,” he adds. “When you have a multivitamin that’s multipurpose, that’s going to be attractive to a lot of customers. [It’s a preference] I expect will continue to grow.”

Szelążek at Euromonitor said similar, noting that “consumers are moving towards products which are supposed to target more than just one condition” and that “we have noticed that there is an increased demand for combination products and multivitamins.”

Consumers like the convenience of multivitamins for brain health, SPINS’s Resetar agrees. “Multivitamins are a quick method of receiving necessary nutrients in a small, compact package, making it popular for a society of movers and shakers.”

Of brain health multivitamins, she says, “Much of their growth can be traced back to the trend of overall wellness that was brought on by the pandemic. It is multifunctional to attack many different health focuses. We can expect to see a growth in vitamins that designate different areas of health in addition to their other marketed benefits, including immunity, digestive, and cognitive.” Also, she says, “Growth spurs innovation, and with the growth in multivitamins, we expect to see changes in their form (gummies, candy, powder, liquid), in their packaging, and in what they offer.”

IRI highlights one category leader as evidence. “Focus Factor is a great example of this kind of product, and it grew 47% in 2021 versus 2020,” analysts say. “[It’s] a bit pricey but delivers on the promise of a solid multivitamin with the blend of brain-supportive ingredients.”

When it comes to ingredients selling especially well in the U.S. mainstream cognitive health supplements market, one ingredient with notable growth was phosphatidylserine (PS).

Per SPINS multioutlet channel tracking, PS sales in the mainstream cognitive health supplements market in the U.S. grew 91% in the year ending October 31, 2021, reaching $96 million compared to $50 million a year ago.

“PS represents a trending ingredient in the brain health space, clinically demonstrated to support and improve mind and body performance for consumers of all ages,” says Eran Ivanir, director of clinical development, IFF Health (New York). “A natural building block of our tissues, found in every cell membrane, PS has been shown to play a crucial role in the structure and function of the brain, as well as in muscles and other tissues.”

Laurentia Guesman, business manager, AIDP Inc. (City of Industry, CA), discusses the role of PS in brain health. “PS is a vital phospholipid essential to memory and cognitive health. It is mainly concentrated in the brain and nerves, and is essential to nerve-cell functions. Among other functions, PS dramatically boosts protein kinase C (PKC) activity within the neuronal membranes. PKC is an intracellular messenger enzyme that regulates the release of acetylcholine and dopamine, neurotransmitters that are critical to learning and memory.”

Holtby at Soft Gel Technologies says, “Several multicenter, double-blind, placebo-controlled trials on patients with Alzheimer’s disease have suggested that PS improves cognitive performance. PS is a building block for brain cell membranes and protects the function of brain cells by stabilizing the membranes of the cells. Healthy, well-structured cell membranes promote optimal brain cell performance. Brain cell activity is important for proper memory recall. PS may increase brain function by limiting the deterioration of cell membranes that contribute to brain aging.”

He adds, “It has been demonstrated in clinical trials to improve memory, concentration, word recall, and mood in middle-aged and elderly subjects with dementia and age-related cognitive decline. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists.”

Guesman and others point out that “PS is the only dietary ingredient with two FDA qualified health claims related to reducing risk of cognitive dysfunction and dementia in older adults.”

“While many nutraceutical ingredients have been touted for their ability to improve cognitive performance, few have the scientific backing of PS,” adds Holtby.

“PS has proven to be an effective supplement for cognitive health, and those results are attributing to its growth,” agrees SPINS’s Resetar.

The science backing PS is strong—and continues to grow not only on brain-related health concerns such as mood and stress but also sports, skin health, and more.

“Research is absolutely expanding for PS, which has helped drive the increase in sales,” says Mike Petteruti, president and general manager, Chemi Nutra (Austin, TX). “Some of the most notable data we have seen in recent years has been for stress benefits, particularly for cortisol reduction. In addition to stress, we see an ever-expanding base for the cognitive and memory applications of the ingredient as PS has historically been used.”

IFF’s Ivanir points out the benefits of PS for both mental and physical stress. “While PS is most commonly known for its effects on cognitive function, there are other effects that have been identified in humans. For instance, several clinical studies examine the effects of PS on exercise, and it’s shown to improve several different aspects.”

He continues: “Intake of PS is known to lessen the increases in cortisol that are associated with mental stress as well as physical stress (exercise). Since PS is a safe dietary ingredient, supplements containing PS may provide an effective alternative for those seeking to ease day-to-day stress and keep a balanced mood.”

Multivitamins and popular ingredients like phosphatidylserine and bacopa will continue driving interest.

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